State Estimation in the Cerebellum

An exciting hypothesis about the cerebellum is that its role is one of state estimation—a process that combines afferent copies of motor commands with afferent sensory signals to produce a representation of the current status of the peripheral motor system. Sensory inputs alone cannot provide a perfect state signal because of inevitable delays in their afferent pathways. We have recently reported the effects of transcranial magnetic stimulation (TMS) over the ipsilateral cerebellum as healthy subjects made rapid reaching movements towards visually defined targets (Miall et al. in PLoS Biology 5:2733–2744, 2007). Errors in the initial direction and in the final finger position of this reachto-target movement were consistent with the reaching movements being planned and initiated from an estimated hand position that was about 138 ms out of date. This interval is consistent with estimates of the delays in sensory motor pathways that would inform the central nervous system of the peripheral status. We now report new data using the same paradigm, testing the effects of varying the TMS stimulus train from one, two, or three pulses. We show that the errors in movement are relatively insensitive to the TMS pulse-train duration. The estimated time interval by which the hand position is mislocalized varied by only 12 ms as the TMS train duration increased by 100 ms. Thus, this interval is likely to reflect physiological processes within the cerebellum rather than the TMSstimulus duration. This new evidence supports our earlier claim that the cerebellum is responsible for predictively updating a central state estimate over an interval of about 120–140 ms. Dysfunction of the cerebellum, whether through disease or experimental procedures, leads to motor errors consistent with a loss of knowledge of the true state of the motor system

The cerebellum and motor dysfunction in neuropsychiatric disorders

The cerebellum is densely interconnected with sensory-motor areas of the cerebral cortex, and in man, the great expansion of the association areas of cerebral cortex is also paralleled by an expansion of the lateral cerebellar hemispheres. It is therefore likely that these circuits contribute to non-motor cognitive functions, but this is still a controversial issue. One approach is to examine evidence from neuropsychiatric disorders of cerebellar involvement. In this review, we narrow this search to test whether there is evidence of motor dysfunction associated with neuropsychiatric disorders consistent with disruption of cerebellar motor function. While we do find such evidence, especially in autism, schizophrenia and dyslexia, we caution that the restricted set of motor symptoms does not suggest global cerebellar dysfunction. Moreover, these symptoms may also reflect involvement of other, extra-cerebellar circuits and detailed examination of specific sub groups of individuals within each disorder may help to relate such motor symptoms to cerebellar morphology

Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Predictive information and error processing : the role of medial-frontal cortex during motor control

We have recently provided evidence that an error-related negativity (ERN), an ERP component generated within medial-frontal cortex, is elicited by errors made during the performance of a continuous tracking task (O.E. Krigolson & C.B. Holroyd, 2006). In the present study we conducted two experiments to investigate the ability of the medial-frontal error system to evaluate predictive error information. In two experiments participants used a joystick to perform a computer-based continuous tracking task in which some tracking errors were inevitable. In both experiments, half of these errors were preceded by a predictive cue. The results of both experiments indicated that an ERN-like waveform was elicited by tracking errors. Furthermore, in both experiments the predicted error waveforms had an earlier peak latency than the unpredicted error waveforms. These results demonstrate that the medial-frontal error system can evaluate predictive error information

Augmenting Sensorimotor Control Using “Goal-Aware” Vibrotactile Stimulation during Reaching and Manipulation Behaviors

We describe two sets of experiments that examine the ability of vibrotactile encoding of simple position error and combined object states (calculated from an optimal controller) to enhance performance of reaching and manipulation tasks in healthy human adults. The goal of the first experiment (tracking) was to follow a moving target with a cursor on a computer screen. Visual and/or vibrotactile cues were provided in this experiment, and vibrotactile feedback was redundant with visual feedback in that it did not encode any information above and beyond what was already available via vision. After only 10 minutes of practice using vibrotactile feedback to guide performance, subjects tracked the moving target with response latency and movement accuracy values approaching those observed under visually guided reaching. Unlike previous reports on multisensory enhancement, combining vibrotactile and visual feedback of performance errors conferred neither positive nor negative effects on task performance. In the second experiment (balancing), vibrotactile feedback encoded a corrective motor command as a linear combination of object states (derived from a linear-quadratic regulator implementing a trade-off between kinematic and energetic performance) to teach subjects how to balance a simulated inverted pendulum. Here, the tactile feedback signal differed from visual feedback in that it provided information that was not readily available from visual feedback alone. Immediately after applying this novel “goal-aware” vibrotactile feedback, time to failure was improved by a factor of three. Additionally, the effect of vibrotactile training persisted after the feedback was removed. These results suggest that vibrotactile encoding of appropriate combinations of state information may be an effective form of augmented sensory feedback that can be applied, among other purposes, to compensate for lost or compromised proprioception as commonly observed, for example, in stroke survivors

Adaptive intermittent control: A computational model explaining motor intermittency observed in human behavior

It is a fundamental question how our brain performs a given motor task in a real-time fashion with the slow sensorimotor system. Computational theory proposed an influential idea of feed-forward control, but it has mainly treated the case that the movement is ballistic (such as reaching) because the motor commands should be calculated in advance of movement execution. As a possible mechanism for operating feed-forward control in continuous motor tasks (such as target tracking), we propose a control model called "adaptive intermittent control" or "segmented control," that brain adaptively divides the continuous time axis into discrete segments and executes feed-forward control in each segment. The idea of intermittent control has been proposed in the fields of control theory, biological modeling and nonlinear dynamical system. Compared with these previous models, the key of the proposed model is that the system speculatively determines the segmentation based on the future prediction and its uncertainty. The result of computer simulation showed that the proposed model realized faithful visuo-manual tracking with realistic sensorimotor delays and with less computational costs (i.e., with fewer number of segments). Furthermore, it replicated "motor intermittency", that is, intermittent discontinuities commonly observed in human movement trajectories. We discuss that the temporally segmented control is an inevitable strategy for brain which has to achieve a given task with small computational (or cognitive) cost, using a slow control system in an uncertain variable environment, and the motor intermittency is the side-effect of this strategy

Population-scale organization of cerebellar granule neuron signaling during a visuomotor behavior.

Granule cells at the input layer of the cerebellum comprise over half the neurons in the human brain and are thought to be critical for learning. However, little is known about granule neuron signaling at the population scale during behavior. We used calcium imaging in awake zebrafish during optokinetic behavior to record transgenically identified granule neurons throughout a cerebellar population. A significant fraction of the population was responsive at any given time. In contrast to core precerebellar populations, granule neuron responses were relatively heterogeneous, with variation in the degree of rectification and the balance of positive versus negative changes in activity. Functional correlations were strongest for nearby cells, with weak spatial gradients in the degree of rectification and the average sign of response. These data open a new window upon cerebellar function and suggest granule layer signals represent elementary building blocks under-represented in core sensorimotor pathways, thereby enabling the construction of novel patterns of activity for learning

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)